Dysmetabolic Iron Overload Syndrome (DIOS)

by | Jan 28, 2025 | Articles, Conditions, General Interest

Dysmetabolic Iron Overload Syndrome (DIOS) is treated very differently from genetic hemochromatosis. The goal is fix the metabolic problem, not aggressively “bleed out” iron.

Here’s the evidence-based, clinically practical approach.

What DIOS actually is

DIOS is characterized by:

  • Mild–moderate iron overload (↑ ferritin, often normal or mildly ↑ TSAT)

  • Normal or low transferrin saturation (often <45%)

  • Iron stored mainly in the liver

  • Strong association with:

    • Insulin resistance

    • Metabolic syndrome

    • Fatty liver (NAFLD / MASLD)

    • Obesity, dyslipidemia

Key mechanism:

Hepcidin resistance, not hepcidin deficiency
→ iron gets trapped in tissues, especially liver macrophages

This is why treatment differs from classic hemochromatosis.

First-line treatment: fix insulin resistance

(This is the cornerstone)

Improving insulin sensitivity reliably lowers ferritin over time.

Nutrition

  • Lower refined carbohydrates and fructose (especially soda, fruit juice)

  • Mediterranean or low-glycemic diet

  • Adequate protein

  • Avoid excess calories

⚠️ Fructose directly increases hepatic iron uptake and worsens NAFLD.

Weight loss

  • Even 5–10% body weight reduction can significantly lower ferritin

  • Liver fat reduction → improved iron handling

Exercise

  • Regular aerobic + resistance training

  • Improves:

    • Insulin sensitivity

    • Hepatic iron export

    • Inflammatory signaling

Treat fatty liver aggressively (if present)

DIOS and fatty liver are tightly linked.

Helpful measures:

  • Weight loss

  • Alcohol reduction or elimination

  • Glycemic control

  • Triglyceride reduction

When liver fat improves, ferritin often falls without any iron-specific intervention.

Alcohol reduction (very important)

Alcohol:

  • Suppresses hepcidin

  • Increases gut iron absorption

  • Synergistically worsens iron-related liver injury

📌 Even “moderate” alcohol can keep ferritin elevated in DIOS.

Phlebotomy: selective and cautious

Unlike hereditary hemochromatosis:

  • Routine phlebotomy is NOT first-line

  • Over-phlebotomy can worsen fatigue and insulin resistance

When phlebotomy may be used:

  • Ferritin persistently >500–700 ng/mL

  • Evidence of liver injury

  • Symptoms clearly correlate with iron burden

  • TSAT rising toward hemochromatosis range

If used:

  • Low-frequency (e.g., every 2–4 months)

  • Stop once ferritin ~100–200 ng/mL

  • Monitor symptoms closely

Avoid unnecessary iron intake

  • Stop iron supplements unless clearly indicated

  • Avoid iron-fortified foods

  • Be cautious with high-dose vitamin C (increases iron absorption)

Address inflammation and oxidative stress

(adjunctive, not primary)

These don’t “remove” iron but reduce iron-related damage.

Common adjuncts used clinically:

  • Omega-3 fatty acids

  • Polyphenols (green tea, curcumin)

  • Adequate magnesium

  • Glycemic control (reduces oxidative stress signaling)

What NOT to do

🚫 Treat like classic hemochromatosis
🚫 Aggressive weekly phlebotomy
🚫 Ignore metabolic syndrome
🚫 Chase ferritin alone without context

Ferritin in DIOS is both:

  • An iron marker

  • An inflammatory/metabolic marker

Monitoring strategy

Typical follow-up includes:

  • Ferritin

  • Transferrin saturation

  • ALT / AST

  • HbA1c or fasting insulin

  • Lipids

Trend matters more than single values.

Bottom line

DIOS is a metabolic disease with iron consequences, not a primary iron-loading disorder.

Best treatment hierarchy:

  1. Insulin resistance reversal

  2. Fatty liver improvement

  3. Alcohol reduction

  4. Selective, limited phlebotomy (if needed)

When metabolism improves, iron often normalizes on its own.


Author

Scott Rollins, MD, is Board Certified with the American Board of Family Practice and the American Board of Anti-Aging and Regenerative Medicine.  He specializes in bioidentical hormone replacement for men and women, thyroid and adrenal disorders, fibromyalgia and other complex medical conditions.  He is founder and medical director of the Integrative Medicine Center of Western Colorado (www.imcwc.com) and Bellezza Laser Aesthetics (www.bellezzalaser.com).   Call (970) 245-6911 for an appointment or more information.

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